My short term plans are to expand on my studies of the relationship between the lysosomal metabolism of cystine and the development of the renal Fanconi syndrome using the techniques and information gained during my fellowship. Fibroblasts from normal individuals and from patients with the inherited disorders, mucolipidosis type II and cystinosis, will be grown in tissue culture. The lysosomes of these cells will be filled with cystine through the use of either cystine dimethyl ester or the mixed disulfide of cysteine and glutathione. Established methods of subcellular fractionation combined with free flow electrophoresis will be used to isolate purified lysosomes from these cells. The lysosomal metabolism of radiolabeled cystine by these various cell types will be compared. Identification of the biochemical abnormality in cytinosis will be related to the clinical manifestations of this disorder. The effects of metals, cystine, and maleic acid on lysosomal sulfhydryl sensitive proteases will be examined since these are all substances associated with the development of the renal Fanconi syndrome. Cathepsin function in fibroblasts from patients with idiopathic Fanconi syndrme will also be examined. Eventually, the experience gained during these investigations will help me establish myself as an independent investigator at an academic medical center. My focus will be inherited biochemical abnormalities and their clinical expressions in human disease.